Alternative splicing of the Ca V1.3 channel IQ domain, a molecular switch for Ca 2+-dependent inactivation within auditory hair cells

Yiru Shen, Dejie Yu, Hakim Hiel, Ping Liao, David T. Yue, Paul A. Fuchs, Wah Soong Tuck

Research output: Contribution to journalArticlepeer-review

Abstract

Native Ca V1.3 channels within cochlear hair cells exhibit a surprising lack of Ca 2+-dependent inactivation (CDI), given that heterologously expressed Ca V1.3 channels show marked CDI. To determine whether alternative splicing at the C terminus of the Ca V1.3 gene may produce a hair cell splice variant with weak CDI, we transcript-scanned mRNA obtained from rat cochlea. We found that the alternate use of exon 41 acceptor sites generated a splice variant that lost the calmodulin-binding IQ motif of the C terminus. These Ca V1.3 IQΔ ("IQ deleted") channels exhibited a lack of CDI, which was independent of the type of coexpressed β-subunits. Ca V1.3 IQΔ channel immunoreactivity was preferentially localized to cochlear outer hair cells (OHCs), whereas that of Ca V1.3 IQfull channels (IQ-possessing) labeled inner hair cells (IHCs). The preferential expression of Ca V1.3 IQΔ within OHCs suggests that these channels may play a role in processes such as electromotility or activity-dependent gene transcription rather than neurotransmitter release, which is performed predominantly by IHCs in the cochlea.

Original languageEnglish (US)
Pages (from-to)10690-10699
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number42
DOIs
StatePublished - Oct 18 2006

Keywords

  • Alternative splicing
  • Calcium channels
  • Calcium-dependent inactivation
  • Hair cells
  • L-type calcium channels
  • Splice variant

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Alternative splicing of the Ca <sub>V</sub>1.3 channel IQ domain, a molecular switch for Ca <sup>2+</sup>-dependent inactivation within auditory hair cells'. Together they form a unique fingerprint.

Cite this